Recent findings have stimulated renewed interest in a particular model of individual differences in susceptibility to stress. The model is a genetic one consisting of the Maudsley Reactive (MR) and Maudsley Non-Reactive (MNR) rat strains which have been selectively bred for differences in response to mild stress. Recent research by the Principal Investigator confirms that, in addition to the well-established behavioral differences between the strains, there is a fundamental difference in their cardiovascular response to stress. In addition, related experiments have demonstrated substantial and highly reliable differences in their central and peripheral noradrenergic systems under basal conditions. Thus, there is an association in the strains between stress-responsivity and their central and peripheral NE-systems. To discover if the neurochemical differences between MR and MNR strains are functionally related to their differences in stress-responsivity, the following groups of experiments will be performed: (a) the activation of the NE-system will be compared in MR and MNR rats after acute and chronic stress; (b) the consistency of the correlation between NE-system and stress-responsivity will be examined in unique stocks of specially developed RXNR recombinant-inbred strains; (c) comparisons will be made of MR/MNR cardiovascular response to catecholamine infusions. Finally, the way in which genes have altered the noradrenergic system of MR and MNR will be investigated.